The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

Rodríguez, Milagros Collados; Dybas, Joseph M.; Hughes, Joseph; Weitzman, Matthew D.; Boutell, Chris

doi:10.1016/j.virusres.2020.198015

Cited by 74 publications

(53 citation statements)

References 181 publications

(282 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Promyelocytic leukaemia nuclear bodies (PML-NBs), also referred to as nuclear domains 10 (ND10), or PML oncogenic domains (PODs), are small (0.1–1.0 µm) dynamic nuclear structures made of several constant (PML, SP100, Daxx) or transiently associated proteins, depending on the cell function and/or exposed stress [ 60 , 61 , 62 ]. They respond to varieties of stimuli including apoptosis, senescence viral infections and interferon response [ 63 ].…”

Section: Hsv Immune Evasion Mechanismsmentioning

confidence: 99%

“…Therefore, understanding the underlying mechanisms of HSV-1 chromatinization-induced latency is important. The PML-NBs is organized by protein–protein interaction between SUMOylated proteins and SUMO-interacting motifs (SIMs) [ 61 ]. PML is the key protein responsible for the assembly and maintenance of PML-NBs.…”

Section: Hsv Immune Evasion Mechanismsmentioning

confidence: 99%

“…However, this mechanism to repress HSV-1 gene expression is counteracted by ICP0 through its E3 ubiquitin ligase activity. Using a combination of SUMO-dependent and independent targeting strategies, HSV-1 (ICP0) ubiquitinates and degrades PML and SP100, resulting in the disruption of PML-NBs and the subsequent release of viral genes [ 61 ].…”

Section: Hsv Immune Evasion Mechanismsmentioning

confidence: 99%

See 2 more Smart Citations

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

et al. 2020

View full text Add to dashboard Cite

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

show abstract

Section: Hsv Immune Evasion Mechanismsmentioning

confidence: 99%

Section: Hsv Immune Evasion Mechanismsmentioning

confidence: 99%

Section: Hsv Immune Evasion Mechanismsmentioning

confidence: 99%

See 1 more Smart Citation

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It is known that challenging epithelial cells with HSV1 depletes Sp100 SUMOylated isoforms ( Everett et al, 2009 ), as occurs when UBC9 or PML are silenced by shRNA ( Everett et al, 2006 ). Thus, Sp100 degradation could either be a direct target of ICP0 ( Perusina Lanfranca et al, 2013 ), a viral E3 Ub ligase which preferentially targets SUMOylated proteins for proteasomal degradation [( Boutell et al, 2011 ), reviewed by ( Boutell and Everett, 2013 ; Rodriguez et al, 2020 )], or occur as an indirect consequence of PML disposal by ICP0 ( Tavalai and Stamminger, 2009 ). In any case, dismantling of PML-NB by ICP0 or by PML shRNA silencing has no effect on Sp100A ( Everett et al, 2006 ; Everett et al, 2009 ), advancing that Sp100A transactivating properties may be exploited by HSV1 (see below).…”

Section: The Spatiotemporal Journey Of Sp100 Against Herpesvirusesmentioning

confidence: 99%

The Fate of Speckled Protein 100 (Sp100) During Herpesviruses Infection

Collados Rodríguez

2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The constitutive expression of Speckled-100 (Sp100) is known to restrict the replication of many clinically important DNA viruses. This pre-existing (intrinsic) immune defense to virus infection can be further upregulated upon interferon (IFN) stimulation as a component of the innate immune response. In humans, Sp100 is encoded by a single gene locus, which can produce alternatively spliced isoforms. The widely studied Sp100A, Sp100B, Sp100C and Sp100HMG have functions associated with the transcriptional regulation of viral and cellular chromatin, either directly through their characteristic DNA-binding domains, or indirectly through post-translational modification (PTM) and associated protein interaction networks. Sp100 isoforms are resident component proteins of promyelocytic leukemia-nuclear bodies (PML-NBs), dynamic nuclear sub-structures which regulate host immune defenses against many pathogens. In the case of human herpesviruses, multiple protein antagonists are expressed to relieve viral DNA genome transcriptional silencing imposed by PML-NB and Sp100-derived proteinaceous structures, thereby stimulating viral propagation, pathogenesis, and transmission to new hosts. This review details how different Sp100 isoforms are manipulated during herpesviruses HSV1, VZV, HCMV, EBV, and KSHV infection, identifying gaps in our current knowledge, and highlighting future areas of research.

show abstract

“…RING finger proteins are a large family of proteins containing a C3HC4-type RING domain (RD) (Cys–X2–Cys–X9–39–Cys–Xl–3–His–X2–3–Cys–X2–Cys–X4–48–Cys–X2–Cys; C is cysteine, H is histidine), widely involved in diverse aspects of biological processes of cellular organisms [ 21 , 22 ] and human–virus life cycles [ 23 ] with E3 ubiquitin ligase activity. E3 ubiquitin ligase is a member of an enzymatic cascade for protein ubiquitination, including E1 ubiquitin-activating enzyme and E2 ubiquitin-conjugating enzyme [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Diversity among Five RING Finger Proteins from Carassius Auratus Herpesvirus (CaHV)

Wang

Fei

Zhang

et al. 2021

Viruses

View full text Add to dashboard Cite

Carassius auratus herpesvirus (CaHV) has been identified as a high-virulence pathogenic virus that infects aquatic animals, but the key factor for virus–host interaction is still unclear. Five Really interesting new genes (RING) finger proteins (39L, 52L, 131R, 136L, and 143R) of CaHV were screened to determine structural diversity. RING finger proteins were also predicted in other known fish herpesviruses, with an arrangement and number similar to CaHV. We performed multifaceted analyses of the proteins, including protein sizes, skeleton structures, subcellular localizations, and ubiquitination activities, to determine their precise roles in virus–host interactions. The five proteins were overexpressed and detected different levels of ubiquitination activities, and 143R showed the highest activity. Then, the prokaryotic expressed and purified full-length proteins (131R and 136L), RING domain isolates (131R12–43 and 136L45–87), and RING domain-deleted mutants (131RΔ12–43 and 136LΔ45–87) were prepared to detect their activities through ubiquitination assays. The results indicate that both full-length proteins and their isolates have activities that catalyze ubiquitination, and the full-length proteins possess higher activity than the isolates, but RING domain-deleted mutants lose their activities. Furthermore, the activities of the five proteins were verified as E3 ubiquitin ligase activity, showing that the RING domains determine the ubiquitination activity. These proteins present different subcellular localization. RING domain-deleted mutants showed similar subcellular localization with their full-length proteins, and all the isolates diffused in whole cells. The current results indicate that the sequence outside the RING domain determines subcellular localization and the level of ubiquitination activity, suggesting that the RING finger proteins of fish herpesviruses might have diverse functions in virus–host interaction.

show abstract

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

Cited by 74 publications

References 181 publications

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

The Fate of Speckled Protein 100 (Sp100) During Herpesviruses Infection

Structural and Functional Diversity among Five RING Finger Proteins from Carassius Auratus Herpesvirus (CaHV)

Contact Info

Product

Resources

About